Lair-1-binding agents and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2025179171-A1
Application number	US-202519035609-A
Country	US
Kind code	A1
Filing date	Jan 23, 2025
Priority date	Jun 22, 2020
Publication date	Jun 5, 2025
Grant date	—

Abstract

The present disclosure provides binding agents, such as antibodies, that specifically bind LAIR-1, including human LAIR-1, as well as compositions comprising the binding agents, and methods of their use. The disclosure also provides related polynucleotides and vectors encoding the binding agents and cells comprising the binding agents.

First claim

What is claimed:

1 . A binding agent that specifically binds the extracellular domain of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), wherein: (i) the binding agent binds to human LAIR-1 and to cynomolgus LAIR-1, (ii) the binding agent binds to human LAIR-1 with a dissociation constant (K D ) of less than 1×10 −9 M, and/or (iii) the binding agent binds to cynomolgus LAIR-1 with a K D of less than 1×10 −8 M; and wherein the binding agent is an antibody or an antigen-binding fragment thereof.

2 . A binding agent that specifically binds the extracellular domain of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), wherein the binding agent comprises
(a) a heavy chain variable region (VH) comprising a VH complementarity determining region (CDR)1, a VH CDR2 and a VH CDR3 from SEQ ID NO: 117, and a light chain variable region (VL) comprising a (VL) CDR1, a VL CDR2 and a VL CDR3 from SEQ ID NO:118; or (b) a heavy chain variable region comprising a VH CDR1, a VH CDR2 and a VH CDR3 from SEQ ID NO:119, and a light chain variable region comprising a VL CDR1, a VL CDR2 and a VL CDR3 from SEQ ID NO:120.

3 . A binding agent that specifically binds the extracellular domain of leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), wherein the binding agent comprises:
(a) a heavy chain variable region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:25, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:26, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:27; and
a light chain variable region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:28, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:29, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(b) a heavy chain variable region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:31, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:32, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:27; and
a light chain variable region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:28, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:29, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(c) a heavy chain variable region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:25, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:33, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:27; and
a light chain variable region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:28, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:29, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:30;
(d) a heavy chain variable region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:34, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:26, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:27; and
a light chain variable region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:28, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:29, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:30; or
(e) a heavy chain variable region comprising a VH CDR1 comprising the amino acid sequence of SEQ ID NO:35, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:36, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:37; and
a light chain variable region comprising a VL CDR1 comprising the amino acid sequence of SEQ ID NO:38, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:39, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:40.

4 . The binding agent of claim 2 , wherein:
(a) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:25, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:41, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:27, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:28, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:30; (b) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:31, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:43, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:27, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:28, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:30; (c) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:25, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:44, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:27, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:28, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:30; (d) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:34, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:41, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:27, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:28, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:42, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:30; or (e) the VH CDR1 comprises the amino acid sequence of SEQ ID NO:35, the VH CDR2 comprises the amino acid sequence of SEQ ID NO:45, the VH CDR3 comprises the amino acid sequence of SEQ ID NO:37, the VL CDR1 comprises the amino acid sequence of SEQ ID NO:38, the VL CDR2 comprises the amino acid sequence of SEQ ID NO:39, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO:40.

5 . The binding agent of claim 2 or 3 , wherein the heavy chain variable region has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:117 and/or the light chain variable region has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:118.

6 . The binding agent of claim 2 or 3 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:117 and/or the light chain variable region comprises the amino acid sequence of SEQ ID NO:118.

7 . The binding agent of claim 2 or 4 , wherein the heavy chain variable region has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:119 and/or the light chain variable region has at least 80% sequence identity to the amino acid sequence of SEQ ID NO:120.

8 . The binding agent of claim 2 or 4 , wherein the heavy chain variable region has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:119 and/or the light chain variable region has at least 90% sequence identity to the amino acid sequence of SEQ ID NO:120.

9 . The binding agent of claim 2 or 4 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:119 or the light chain variable region comprises the amino acid sequence of SEQ ID NO:120.

10 . A binding agent that specifically binds the extracellular domain of LAIR-1, wherein the binding agent comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:119 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:120, wherein the binding agent is an antibody or an antigen-binding fragment thereof.

11 . A binding agent that specifically binds the extracellular domain of LAIR-1, wherein the binding agent comprises:
(a) a heavy chain variable region comprising a VH CDR1, a VH CDR2 and a VH CDR3 from SEQ ID NO:115, and a light chain variable region comprising a VL CDR1, a VL CDR2 and a VL CDR3 from SEQ ID NO:116; (b) a heavy chain variable region comprising a VH CDR1, a VH CDR2 and a VH CDR3 from SEQ ID NO:121, and a light ch

Assignees

• Ngm Biopharmaceuticals Inc

Inventors

• Crawley Suzanne Christine
• Fan Bin
• Li Betty Chan
• Rivera Lee Benjamin
• Sissons James Robert
• Sitrin Jonathan
• Wang Yan
• Zhao Xuan

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title